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The Key Involvement of Poly(ADP-Ribosylation) in Defense Against Toxic Agents in Molecular Biology Studies
Final rept. 15 Oct 1988-14 Oct 1991
GEORGETOWN UNIV WASHINGTON DC SCHOOL OF MEDICINE
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PolyADP-ribose polymerase requires DNA for activity, and the catalytic activity of this enzyme is directly coordinated to the number of DNA strand breaks in DNA. Use of molecular techniques and the complete amino acid sequence of the enzyme, established during the past granting period, should allow us to learn considerably more about the mechanism and role of this enzyme in cells exposed to stressful environments. In AIM I. we proposed to extend our preliminary data on the insertion of full-length polymerase cDNA into various inducible and non-inducible expression vectors and retroviral vectors in both sense and antisense orientations. This would allow us to either inhibit i.e. through antisense mRNA expression or intensify the translation of polymerase in a variety of eukaryotic cells. A complementary approach was proposed in AIM ii where various functional domains of the polymerase as well as site-directed mutants were to be constructed into inducible expression vectors to test whether selective inhibitors can be favorably used in cells. Once it was verified that both the engineered mRNAs and appropriate peptides were expressed in in vivo procedures in AIM HI we proposed to test for cytotoxicity and DNA repair potential and mutagenesis repair of the various reconstructed cells obtained in AIMS I AND II. polyADP-ribose polymerase, Toxic agents.
APPROVED FOR PUBLIC RELEASE